Recently, a systemic treatment by the transdermal administration of a medicament such as nitroglycerin, scopolamine, isosorbide dinitrate, etc., has been tried. The transdermal administration has several advantages such as a simple way for administration of a drug, a long duration of efficacy, a less occurence of side effects, avoiding inactivation by a first passage effect through the liver, etc., and is one of administration methods the further application and development of which have been expected.
Nicardipine hydrochloride is a very useful compound having a cerebral vascular dilator activity, a coronary dilator activity, and an anti-hypertension activity and considering these medicinal actions, the transdermal administration can become a very effective administration method for the compound. However, different from nitroglycerin, etc., nicardipine hydrochloride itself has poor permeability in skin transport and hence an effective transdermal formulation of the compound is not obtained by applying conventional transdermal formulations to the compound as it is.
Since epidermal tissue of an animal has a barrier mechanism for preventing invasion of foreign matters, the percutaneous absorption of medicaments largely depends upon the specific properties of the medicaments and is very complicated since it is determined by the interaction among a medicament, a base, and the skin. Accordingly, it is very difficult to estimate a contrivance or preparation for promoting the percutaneous absorption of a medicament poor in percutaneous absorption from a preparation technique of a different medicament.
Under such circumstances, the inventors started the development of a transdermal formulation of nicardipine hydrochloride and as the result of various investigations, the inventors have discovered that a transdermal formulation obtained by compounding a liquid of nicardipine hydrochloride dissolved or suspended in a mixed liquid composed of at least one of the group consisting of propylene glycol, a monohydric alcohol having 2 to 4 carbon atoms, lactic acid, thioglycol, a middle chain fatty acid glyceride, and a sorbitan middle chain fatty acid ester and a urea with a transdermal formulation base is excellent in the percutaneous absorption of nicardipine hydrochloride and based on the discovery, the invention has been accomplished.
It has also been discovered that by adding a crystallizing inhibitor of nicardipine hydrochloride to the aforesaid transdermal formulation, a nicardipine hydrochloride transdermal formulation excellent in stability and percutaneous absorption is obtained.